A minimally invasive multiple marker approach allows highly efficient detection of meningioma tumors

BACKGROUND: The development of effective frameworks that permit an accurate diagnosis of tumors, especially in their early stages, remains a grand challenge in the field of bioinformatics. Our approach uses statistical learning techniques applied to multiple antigen tumor antigen markers utilizing the immune system as a very sensitive marker of molecular pathological processes. For validation purposes we choose the intracranial meningioma tumors as model system since they occur very frequently, are mostly benign, and are genetically stable. RESULTS: A total of 183 blood samples from 93 meningioma patients (WHO stages I-III) and 90 healthy controls were screened for seroreactivity with a set of 57 meningioma-associated antigens. We tested several established statistical learning methods on the resulting reactivity patterns using 10-fold cross validation. The best performance was achieved by Naïve Bayes Classifiers. With this classification method, our framework, called Minimally Invasive Multiple Marker (MIMM) approach, yielded a specificity of 96.2%, a sensitivity of 84.5%, and an accuracy of 90.3%, the respective area under the ROC curve was 0.957. Detailed analysis revealed that prediction performs particularly well on low-grade (WHO I) tumors, consistent with our goal of early stage tumor detection. For these tumors the best classification result with a specificity of 97.5%, a sensitivity of 91.3%, an accuracy of 95.6%, and an area under the ROC curve of 0.971 was achieved using a set of 12 antigen markers only. This antigen set was detected by a subset selection method based on Mutual Information. Remarkably, our study proves that the inclusion of non-specific antigens, detected not only in tumor but also in normal sera, increases the performance significantly, since non-specific antigens contribute additional diagnostic information. CONCLUSION: Our approach offers the possibility to screen members of risk groups as a matter of routine such that tumors hopefully can be diagnosed immediately after their genesis. The early detection will finally result in a higher cure- and lower morbidity-rate

GraBCas: a bioinformatics tool for score-based prediction of Caspase- and Granzyme B-cleavage sites in protein sequences

Caspases and granzyme B are proteases that share the primary specificity to cleave at the carboxyl terminal of aspartate residues in their substrates. Both, caspases and granzyme B are enzymes that are involved in fundamental cellular processes and play a central role in apoptotic cell death. Although various targets are described, many substrates still await identification and many cleavage sites of known substrates are not identified or experimentally verified. A more comprehensive knowledge of caspase and granzyme B substrates is essential to understand the biological roles of these enzymes in more detail. The relatively high variability in cleavage site recognition sequence often complicates the identification of cleavage sites. As of yet there is no software available that allows identification of caspase and/or granzyme with cleavage sites differing from the consensus sequence. Here, we present a bioinformatics tool ‘GraBCas’ that provides score-based prediction of potential cleavage sites for the caspases 1–9 and granzyme B including an estimation of the fragment size. We tested GraBCas on already known substrates and showed its usefulness for protein sequence analysis. GraBCas is available at

SePaCS—a web-based application for classification of seroreactivity profiles

Immunogenic antigen sets possess high potential for minimally invasive disease detection and monitoring. For various diseases, including cancer, appropriate antigen sets have already been detected in blood sera of patients. Typically, a large number of sera from diseased and unaffected persons is screened for the antigens of interest. Sophisticated statistical learning approaches are trained on the resulting data set to classify sera as either tumor or normal sera. We developed a web-based application, called ‘Seroreactivity Profile Classification Service’ (SePaCS) that enables clinical groups to carry out analyzes of training sets and predictions of unclassified seroreactivity profiles with minimal effort. SePaCS provides a broad range of classification methods: four versions of a Naïve Bayes Classifier, Support Vector Machines with a radial basis function kernel, Linear Discriminant Analysis, and Diagonal Discriminant Analysis. The computed results are summarized in a PDF file. We demonstrate the functionality of SePaCS exemplarily for meningioma, a generally benign intracranial tumor. As a second example, we evaluated SePaCS on glioma, a malignant brain tumor. SePaCS is freely available at http://www.bioinf.uni-sb.de/sepacs

GeneTrail—advanced gene set enrichment analysis

We present a comprehensive and efficient gene set analysis tool, called ‘GeneTrail’ that offers a rich functionality and is easy to use. Our web-based application facilitates the statistical evaluation of high-throughput genomic or proteomic data sets with respect to enrichment of functional categories. GeneTrail covers a wide variety of biological categories and pathways, among others KEGG, TRANSPATH, TRANSFAC, and GO. Our web server provides two common statistical approaches, ‘Over-Representation Analysis’ (ORA) comparing a reference set of genes to a test set, and ‘Gene Set Enrichment Analysis’ (GSEA) scoring sorted lists of genes. Besides other newly developed features, GeneTrail's statistics module includes a novel dynamic-programming algorithm that improves the P-value computation of GSEA methods considerably. GeneTrail is freely accessible at http://genetrail.bioinf.uni-sb.d

prediction of Caspase- and Granzyme B-cleavage

sites in protein sequence